A metabolite of an anabolic steroid norchlorotestosterone acetate (NClTA) was successfully synthesized and characterized by 1H NMR and 13C NMR spectroscopy and single-crystal X-ray diffraction. The position of the chlorine substituent and the absolute configuration of the molecule were established.
Supporting information
CCDC reference: 2130048
Data collection: APEX3 (Bruker, 2016); cell refinement: SAINT (Bruker, 2016); data reduction: SAINT (Bruker, 2016); program(s) used to solve structure: SHELXT (Sheldrick, 2015); program(s) used to refine structure: SHELXL (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).
4-Chloroandrost-4-ene-3,17-dione
top
Crystal data top
C18H23ClO2 | Dx = 1.308 Mg m−3 |
Mr = 306.81 | Cu Kα radiation, λ = 1.54178 Å |
Orthorhombic, P212121 | Cell parameters from 9974 reflections |
a = 7.4379 (4) Å | θ = 4.4–70.2° |
b = 12.7142 (6) Å | µ = 2.18 mm−1 |
c = 16.4790 (8) Å | T = 100 K |
V = 1558.37 (13) Å3 | Block, clear light colourless |
Z = 4 | 0.05 × 0.01 × 0.01 mm |
F(000) = 656 | |
Data collection top
BRUKER D8 VENTURE diffractometer | 2907 independent reflections |
Radiation source: X-ray tube, Micro focus tube | 2787 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.031 |
Detector resolution: 10.4167 pixels mm-1 | θmax = 70.1°, θmin = 4.4° |
ω and φ scans | h = −9→9 |
Absorption correction: multi-scan (SADABS; Krause et al., 2015) | k = −15→15 |
Tmin = 0.678, Tmax = 0.753 | l = −20→19 |
18469 measured reflections | |
Refinement top
Refinement on F2 | Hydrogen site location: inferred from neighbouring sites |
Least-squares matrix: full | H-atom parameters constrained |
R[F2 > 2σ(F2)] = 0.024 | w = 1/[σ2(Fo2) + (0.0383P)2 + 0.2052P] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.065 | (Δ/σ)max = 0.001 |
S = 1.04 | Δρmax = 0.17 e Å−3 |
2907 reflections | Δρmin = −0.18 e Å−3 |
191 parameters | Absolute structure: Flack x determined using 1150 quotients
[(I+)-(I-)]/[(I+)+(I-)]
(Parsons et al., 2013) |
0 restraints | Absolute structure parameter: 0.029 (4) |
Primary atom site location: dual | |
Special details top
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes)
are estimated using the full covariance matrix. The cell esds are taken
into account individually in the estimation of esds in distances, angles
and torsion angles; correlations between esds in cell parameters are only
used when they are defined by crystal symmetry. An approximate (isotropic)
treatment of cell esds is used for estimating esds involving l.s. planes. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
Cl1 | 0.53413 (6) | −0.00451 (3) | 0.67248 (3) | 0.02851 (13) | |
O1 | 0.1878 (2) | −0.02569 (11) | 0.74872 (9) | 0.0345 (3) | |
O2 | 0.3004 (2) | 0.70098 (13) | 0.43229 (10) | 0.0401 (4) | |
C1 | 0.2157 (3) | 0.06557 (15) | 0.73085 (11) | 0.0242 (4) | |
C5 | 0.2976 (2) | 0.36358 (14) | 0.60909 (11) | 0.0191 (3) | |
H5 | 0.259997 | 0.323792 | 0.559582 | 0.023* | |
C6 | 0.1640 (2) | 0.45474 (14) | 0.62010 (12) | 0.0228 (4) | |
H6A | 0.188454 | 0.489661 | 0.672646 | 0.027* | |
H6B | 0.040622 | 0.425670 | 0.622443 | 0.027* | |
C17 | 0.3824 (2) | 0.09845 (14) | 0.68886 (11) | 0.0214 (4) | |
C3 | 0.0974 (2) | 0.24336 (14) | 0.69275 (11) | 0.0234 (4) | |
H3A | 0.017607 | 0.300838 | 0.711313 | 0.028* | |
H3B | 0.051866 | 0.217948 | 0.639818 | 0.028* | |
C7 | 0.1726 (2) | 0.53763 (15) | 0.55206 (12) | 0.0243 (4) | |
H7A | 0.128879 | 0.506525 | 0.500636 | 0.029* | |
H7B | 0.093792 | 0.597774 | 0.565909 | 0.029* | |
C4 | 0.2882 (2) | 0.28617 (13) | 0.68182 (11) | 0.0193 (3) | |
H4 | 0.319484 | 0.326567 | 0.731938 | 0.023* | |
C16 | 0.4260 (2) | 0.19893 (13) | 0.67251 (11) | 0.0206 (3) | |
C13 | 0.4912 (2) | 0.40302 (14) | 0.59430 (11) | 0.0197 (4) | |
H13 | 0.534533 | 0.439779 | 0.644250 | 0.024* | |
C9 | 0.4042 (3) | 0.64247 (15) | 0.46663 (12) | 0.0278 (4) | |
C15 | 0.6121 (3) | 0.23322 (15) | 0.64898 (13) | 0.0277 (4) | |
H15A | 0.684117 | 0.170390 | 0.634705 | 0.033* | |
H15B | 0.670068 | 0.267385 | 0.696210 | 0.033* | |
C2 | 0.0914 (3) | 0.15384 (15) | 0.75394 (12) | 0.0263 (4) | |
H2A | 0.125680 | 0.180934 | 0.808097 | 0.032* | |
H2B | −0.033061 | 0.126618 | 0.757601 | 0.032* | |
C8 | 0.3650 (2) | 0.57594 (14) | 0.54125 (11) | 0.0215 (4) | |
C18 | 0.4268 (3) | 0.64214 (15) | 0.61467 (12) | 0.0255 (4) | |
H18A | 0.340763 | 0.699209 | 0.624110 | 0.038* | |
H18B | 0.545813 | 0.671945 | 0.603545 | 0.038* | |
H18C | 0.433172 | 0.597296 | 0.662951 | 0.038* | |
C14 | 0.6134 (2) | 0.30946 (15) | 0.57747 (12) | 0.0262 (4) | |
H14A | 0.737587 | 0.334569 | 0.567856 | 0.031* | |
H14B | 0.572060 | 0.272622 | 0.527940 | 0.031* | |
C12 | 0.4880 (2) | 0.48125 (14) | 0.52440 (11) | 0.0221 (4) | |
H12 | 0.435207 | 0.443399 | 0.476847 | 0.027* | |
C10 | 0.5982 (3) | 0.62344 (17) | 0.44187 (13) | 0.0336 (5) | |
H10A | 0.671889 | 0.687004 | 0.451795 | 0.040* | |
H10B | 0.605681 | 0.605168 | 0.383565 | 0.040* | |
C11 | 0.6645 (3) | 0.53098 (16) | 0.49478 (13) | 0.0302 (4) | |
H11A | 0.735925 | 0.480383 | 0.462438 | 0.036* | |
H11B | 0.738045 | 0.556310 | 0.540879 | 0.036* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
Cl1 | 0.0383 (2) | 0.0235 (2) | 0.0237 (2) | 0.00946 (18) | 0.00264 (17) | 0.00324 (19) |
O1 | 0.0444 (8) | 0.0246 (7) | 0.0345 (8) | −0.0055 (6) | 0.0073 (7) | 0.0060 (6) |
O2 | 0.0503 (9) | 0.0395 (8) | 0.0305 (8) | 0.0078 (8) | 0.0007 (7) | 0.0141 (7) |
C1 | 0.0307 (9) | 0.0246 (9) | 0.0173 (9) | −0.0043 (8) | −0.0020 (7) | −0.0001 (7) |
C5 | 0.0164 (8) | 0.0212 (8) | 0.0198 (8) | −0.0009 (7) | 0.0004 (7) | −0.0029 (7) |
C6 | 0.0190 (8) | 0.0252 (9) | 0.0241 (10) | 0.0023 (7) | 0.0021 (7) | 0.0019 (7) |
C17 | 0.0263 (9) | 0.0229 (8) | 0.0151 (8) | 0.0034 (7) | −0.0013 (7) | −0.0013 (7) |
C3 | 0.0189 (8) | 0.0237 (9) | 0.0275 (10) | −0.0015 (7) | 0.0027 (7) | −0.0004 (7) |
C7 | 0.0212 (8) | 0.0279 (9) | 0.0237 (9) | 0.0042 (7) | −0.0011 (7) | 0.0033 (7) |
C4 | 0.0176 (7) | 0.0199 (8) | 0.0203 (8) | −0.0011 (6) | 0.0008 (7) | −0.0025 (7) |
C16 | 0.0206 (8) | 0.0229 (8) | 0.0183 (8) | 0.0011 (6) | −0.0004 (7) | −0.0018 (7) |
C13 | 0.0171 (8) | 0.0208 (8) | 0.0212 (9) | −0.0008 (7) | 0.0026 (6) | −0.0022 (7) |
C9 | 0.0387 (10) | 0.0246 (9) | 0.0202 (9) | −0.0019 (8) | 0.0012 (8) | −0.0007 (8) |
C15 | 0.0186 (8) | 0.0259 (9) | 0.0386 (11) | 0.0029 (7) | 0.0001 (8) | 0.0025 (8) |
C2 | 0.0260 (9) | 0.0277 (9) | 0.0253 (9) | −0.0046 (7) | 0.0060 (7) | 0.0006 (8) |
C8 | 0.0241 (9) | 0.0224 (8) | 0.0179 (8) | 0.0016 (7) | 0.0004 (7) | 0.0008 (7) |
C18 | 0.0320 (10) | 0.0232 (9) | 0.0211 (9) | 0.0018 (7) | −0.0011 (7) | 0.0001 (7) |
C14 | 0.0192 (8) | 0.0261 (9) | 0.0332 (10) | 0.0025 (7) | 0.0069 (8) | −0.0001 (8) |
C12 | 0.0214 (8) | 0.0242 (9) | 0.0207 (9) | −0.0007 (7) | 0.0031 (6) | −0.0026 (7) |
C10 | 0.0411 (11) | 0.0313 (11) | 0.0285 (10) | −0.0027 (9) | 0.0117 (9) | 0.0048 (8) |
C11 | 0.0281 (9) | 0.0302 (10) | 0.0323 (11) | −0.0007 (8) | 0.0109 (8) | 0.0021 (8) |
Geometric parameters (Å, º) top
Cl1—C17 | 1.7493 (17) | C13—C14 | 1.523 (2) |
O1—C1 | 1.215 (2) | C13—C12 | 1.522 (3) |
O2—C9 | 1.212 (3) | C9—C8 | 1.521 (3) |
C1—C17 | 1.480 (3) | C9—C10 | 1.519 (3) |
C1—C2 | 1.503 (3) | C15—H15A | 0.9900 |
C5—H5 | 1.0000 | C15—H15B | 0.9900 |
C5—C6 | 1.538 (2) | C15—C14 | 1.526 (3) |
C5—C4 | 1.552 (2) | C2—H2A | 0.9900 |
C5—C13 | 1.544 (2) | C2—H2B | 0.9900 |
C6—H6A | 0.9900 | C8—C18 | 1.544 (3) |
C6—H6B | 0.9900 | C8—C12 | 1.538 (2) |
C6—C7 | 1.540 (3) | C18—H18A | 0.9800 |
C17—C16 | 1.345 (2) | C18—H18B | 0.9800 |
C3—H3A | 0.9900 | C18—H18C | 0.9800 |
C3—H3B | 0.9900 | C14—H14A | 0.9900 |
C3—C4 | 1.530 (2) | C14—H14B | 0.9900 |
C3—C2 | 1.521 (3) | C12—H12 | 1.0000 |
C7—H7A | 0.9900 | C12—C11 | 1.537 (2) |
C7—H7B | 0.9900 | C10—H10A | 0.9900 |
C7—C8 | 1.522 (3) | C10—H10B | 0.9900 |
C4—H4 | 1.0000 | C10—C11 | 1.544 (3) |
C4—C16 | 1.518 (2) | C11—H11A | 0.9900 |
C16—C15 | 1.502 (3) | C11—H11B | 0.9900 |
C13—H13 | 1.0000 | | |
| | | |
O1—C1—C17 | 121.74 (18) | C16—C15—H15A | 109.0 |
O1—C1—C2 | 123.14 (18) | C16—C15—H15B | 109.0 |
C17—C1—C2 | 115.01 (15) | C16—C15—C14 | 112.91 (15) |
C6—C5—H5 | 107.2 | H15A—C15—H15B | 107.8 |
C6—C5—C4 | 110.95 (14) | C14—C15—H15A | 109.0 |
C6—C5—C13 | 112.12 (14) | C14—C15—H15B | 109.0 |
C4—C5—H5 | 107.2 | C1—C2—C3 | 111.88 (15) |
C13—C5—H5 | 107.2 | C1—C2—H2A | 109.2 |
C13—C5—C4 | 111.73 (14) | C1—C2—H2B | 109.2 |
C5—C6—H6A | 108.8 | C3—C2—H2A | 109.2 |
C5—C6—H6B | 108.8 | C3—C2—H2B | 109.2 |
C5—C6—C7 | 113.78 (15) | H2A—C2—H2B | 107.9 |
H6A—C6—H6B | 107.7 | C7—C8—C18 | 111.28 (15) |
C7—C6—H6A | 108.8 | C7—C8—C12 | 109.28 (15) |
C7—C6—H6B | 108.8 | C9—C8—C7 | 116.95 (16) |
C1—C17—Cl1 | 113.65 (13) | C9—C8—C18 | 105.85 (15) |
C16—C17—Cl1 | 121.62 (14) | C9—C8—C12 | 100.08 (14) |
C16—C17—C1 | 124.31 (16) | C12—C8—C18 | 113.01 (15) |
H3A—C3—H3B | 107.9 | C8—C18—H18A | 109.5 |
C4—C3—H3A | 109.3 | C8—C18—H18B | 109.5 |
C4—C3—H3B | 109.3 | C8—C18—H18C | 109.5 |
C2—C3—H3A | 109.3 | H18A—C18—H18B | 109.5 |
C2—C3—H3B | 109.3 | H18A—C18—H18C | 109.5 |
C2—C3—C4 | 111.81 (15) | H18B—C18—H18C | 109.5 |
C6—C7—H7A | 109.6 | C13—C14—C15 | 110.60 (15) |
C6—C7—H7B | 109.6 | C13—C14—H14A | 109.5 |
H7A—C7—H7B | 108.2 | C13—C14—H14B | 109.5 |
C8—C7—C6 | 110.07 (15) | C15—C14—H14A | 109.5 |
C8—C7—H7A | 109.6 | C15—C14—H14B | 109.5 |
C8—C7—H7B | 109.6 | H14A—C14—H14B | 108.1 |
C5—C4—H4 | 107.5 | C13—C12—C8 | 112.60 (14) |
C3—C4—C5 | 111.00 (14) | C13—C12—H12 | 106.5 |
C3—C4—H4 | 107.5 | C13—C12—C11 | 119.74 (15) |
C16—C4—C5 | 110.76 (14) | C8—C12—H12 | 106.5 |
C16—C4—C3 | 112.21 (14) | C11—C12—C8 | 104.11 (14) |
C16—C4—H4 | 107.5 | C11—C12—H12 | 106.5 |
C17—C16—C4 | 120.72 (15) | C9—C10—H10A | 110.6 |
C17—C16—C15 | 123.32 (16) | C9—C10—H10B | 110.6 |
C15—C16—C4 | 115.87 (14) | C9—C10—C11 | 105.83 (16) |
C5—C13—H13 | 108.8 | H10A—C10—H10B | 108.7 |
C14—C13—C5 | 109.38 (14) | C11—C10—H10A | 110.6 |
C14—C13—H13 | 108.8 | C11—C10—H10B | 110.6 |
C12—C13—C5 | 108.50 (14) | C12—C11—C10 | 102.70 (16) |
C12—C13—H13 | 108.8 | C12—C11—H11A | 111.2 |
C12—C13—C14 | 112.45 (15) | C12—C11—H11B | 111.2 |
O2—C9—C8 | 126.60 (18) | C10—C11—H11A | 111.2 |
O2—C9—C10 | 125.27 (19) | C10—C11—H11B | 111.2 |
C10—C9—C8 | 108.13 (16) | H11A—C11—H11B | 109.1 |
| | | |
Cl1—C17—C16—C4 | 175.86 (13) | C7—C8—C12—C11 | 166.87 (15) |
Cl1—C17—C16—C15 | −7.7 (3) | C4—C5—C6—C7 | 177.20 (14) |
O1—C1—C17—Cl1 | −2.6 (2) | C4—C5—C13—C14 | 59.07 (19) |
O1—C1—C17—C16 | −175.31 (19) | C4—C5—C13—C12 | −177.92 (14) |
O1—C1—C2—C3 | −150.53 (19) | C4—C3—C2—C1 | −56.7 (2) |
O2—C9—C8—C7 | 30.3 (3) | C4—C16—C15—C14 | −48.3 (2) |
O2—C9—C8—C18 | −94.3 (2) | C16—C15—C14—C13 | 53.9 (2) |
O2—C9—C8—C12 | 148.1 (2) | C13—C5—C6—C7 | 51.5 (2) |
O2—C9—C10—C11 | −171.2 (2) | C13—C5—C4—C3 | −176.96 (14) |
C1—C17—C16—C4 | −12.0 (3) | C13—C5—C4—C16 | −51.60 (19) |
C1—C17—C16—C15 | 164.43 (18) | C13—C12—C11—C10 | −165.63 (16) |
C5—C6—C7—C8 | −52.9 (2) | C9—C8—C12—C13 | 174.71 (15) |
C5—C4—C16—C17 | −136.86 (17) | C9—C8—C12—C11 | 43.51 (18) |
C5—C4—C16—C15 | 46.5 (2) | C9—C10—C11—C12 | 18.2 (2) |
C5—C13—C14—C15 | −59.3 (2) | C2—C1—C17—Cl1 | 173.68 (13) |
C5—C13—C12—C8 | 58.98 (19) | C2—C1—C17—C16 | 1.0 (3) |
C5—C13—C12—C11 | −178.21 (16) | C2—C3—C4—C5 | 170.25 (14) |
C6—C5—C4—C3 | 57.13 (18) | C2—C3—C4—C16 | 45.7 (2) |
C6—C5—C4—C16 | −177.52 (14) | C8—C9—C10—C11 | 8.9 (2) |
C6—C5—C13—C14 | −175.66 (15) | C8—C12—C11—C10 | −38.77 (19) |
C6—C5—C13—C12 | −52.7 (2) | C18—C8—C12—C13 | 62.56 (19) |
C6—C7—C8—C9 | 168.92 (15) | C18—C8—C12—C11 | −68.63 (19) |
C6—C7—C8—C18 | −69.28 (19) | C14—C13—C12—C8 | −179.90 (15) |
C6—C7—C8—C12 | 56.2 (2) | C14—C13—C12—C11 | −57.1 (2) |
C17—C1—C2—C3 | 33.2 (2) | C12—C13—C14—C15 | −179.92 (15) |
C17—C16—C15—C14 | 135.14 (19) | C10—C9—C8—C7 | −149.86 (17) |
C3—C4—C16—C17 | −12.2 (2) | C10—C9—C8—C18 | 85.56 (18) |
C3—C4—C16—C15 | 171.12 (16) | C10—C9—C8—C12 | −32.04 (19) |
C7—C8—C12—C13 | −61.93 (19) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
C2—H2A···O2i | 0.99 | 2.60 | 3.563 (2) | 165 |
C10—H10A···O2ii | 0.99 | 2.57 | 3.398 (3) | 141 |
C18—H18B···O2ii | 0.98 | 2.56 | 3.507 (3) | 163 |
C10—H10B···O1iii | 0.99 | 2.48 | 3.443 (3) | 164 |
C4—H4···Cl1iv | 1.00 | 2.88 | 3.8202 (18) | 158 |
Symmetry codes: (i) −x+1/2, −y+1, z+1/2; (ii) x+1/2, −y+3/2, −z+1; (iii) x+1/2, −y+1/2, −z+1; (iv) −x+1, y+1/2, −z+3/2. |
Percentage contributions of the most relevant atom–atom contacts to the
Hirshfeld surface in the title structure topAtom-atom interaction | Percentage |
H···H | 56.2 |
H···O/O···H | 22.8 |
H···Cl/Cl···H | 13.7 |
H···C/C···H | 5.6 |
Cl···O/O···Cl | 1.6 |
Cl···C/C···Cl | 0.2 |